Evaluate the Efficacy of Anti-Jak1 Inhibitors as Treatment for Patients With Aicardi-Goutières Syndrome

NCT ID: NCT06898372

Last Updated: 2025-03-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-04-07
• Study Completion Date: 2024-12-18

Brief Summary

Aicardi-Goutières Syndrome (AGS) is a hereditary multisystem autoinflammatory disorder that predominantly affects the central nervous system. It is characterized by severe neurological disability and chronic inflammation caused by the persistent overproduction of type I interferon. To date, nine causative genes of AGS have been identified, each of which can lead to classic AGS presentations, atypical forms, or other manifestations that do not meet the formal diagnostic criteria for AGS and are referred to as "AGS-related interferonopathies." Janus Kinase 1 (JAK1) inhibitors, including Baricitinib and Ruxolitinib, offer a promising therapeutic strategy for Aicardi-Goutières Syndrome (AGS) by directly targeting the central pathogenic pathway of the disease.

Patients treated with JAK1 inhibitors for AGS have shown significant improvement in systemic symptoms, though the effect on neurological symptoms and brain imaging remains unclear.

The aim of this project is to retrospectively analyze the efficacy, particularly on neurological symptoms and brain imaging, and the safety of JAK1 inhibitor treatment in AGS patients treated at Italian tertiary centers. Data will be collected before starting the therapy and during follow-up at 6, 12, 18, and 24 months, where available.

Preliminary data collection was carried out through a survey conducted by the AGS Italy group to assess the number of patients treated with JAK1 inhibitors.

Clinical, brain imaging, genetic, and laboratory data routinely recorded in nine different Italian centers as part of the standard clinical care of these patients will be retrospectively collected and analyzed.

In the second phase of the study, brain MRI data from AGS patients treated with JAK1 inhibitors will be compared to untreated AGS patients matched for age and genotype, in order to evaluate the potential therapeutic efficacy of JAK1 inhibitors on brain imaging compared to the natural clinical progression of the disease.

Through the analysis of the Italian experience, this study could lay the groundwork for drafting a potential consensus on the use of JAK1 inhibitors for the treatment of AGS patients.

Conditions

Aicardi-Goutières Syndrome (AGS)

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Patients with AAGS or AGS-related interferonopathies treated with Anti-Jak1/2

Study group:

1. Patients aged 0 to 25 years

2. Genetic diagnosis of Aicardi-Goutières Syndrome or AGS-related interferonopathies

3. Treatment with Janus Kinase 1/2 (JAK1/2) inhibitors, including Baricitinib and Ruxolitinib

JAK Inhibitor

Intervention Type: DRUG

The retrospective analysis will examine the effects of Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib, on neurological symptoms and brain MRI.

Patients with AGS or AGS-related interferonopathies not treated with Anti-Jak1/2

Control group:

1. Patients aged 0 to 25 years matched with the study cases

2. Genetic diagnosis of Aicardi-Goutières Syndrome or AGS-related interferonopathies with genotype matched to the study cases

3. Not treated with Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib

No interventions assigned to this group

Interventions

JAK Inhibitor

The retrospective analysis will examine the effects of Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib and Ruxolitinib, on neurological symptoms and brain MRI.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients aged 0 to 25 years
• Patients who have been genetically diagnosed with Aicardi-Goutières Syndrome (AGS) or AGS-related interferonopathies For case cohort-Patients treated with Janus Kinase 1/2 (JAK1/2) inhibitors, such as Baricitinib or Ruxolitinib

Exclusion Criteria

• Patients over the age of 25 years
• Patients who have not been genetically diagnosed with Aicardi-Goutières Syndrome (AGS) or AGS-related interferonopathies.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Fondazione Stella Maris

OTHER

Sponsor Role: lead

Responsible Party

Roberta Battini

PHD, Professor, Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

IRCCS Stella Maris Foundation

Pisa, , Italy

Countries

Italy

Other Identifiers

AGS-AntiJak1

Identifier Type: -

Identifier Source: org_study_id